Epigenetic Regulation

Metazoans regulate biological functions in a number of ways, including via gene expression. Epigenetics is the term for regulation of gene expression, other than via changes in the DNA sequence. Modification of DNA or histones by methylation, acetylation, phosphorylation, and ubiquitination affects gene expression and function. Enzymes that chemically modify genomic DNA and histones, as well as epigenetic chromatin remodeling factors, regulate chromatin accessibility and therefore gene expression. Some chromatin remodeling factors contain a chromatin organization modifier domain, or chromodomain, responsible for ATP hydrolysis-dependent chromatin reorganization. Other protein families regulating chromatin structure include bromodomain proteins, plant homeodomain proteins, and the inhibitor of growth family. During the process of stem cell differentiation into terminally differentiated cells, altered expression of chromatin modification enzyme and chromatin remodeling factor genes changes histone modifications, leading to increases or decreases in gene transcription. For example, histone acetyltransferases add acetyl groups to histones. This histone modification is common during transcriptional activation. Epigenetic enzymes also exhibit different expression profiles in tumor cells relative to normal cells, suggesting a role for DNA methylation and chromatin modification in oncogenesis. For example, tumor suppressor genes are often hypermethylated during cancer, which typically causes transcriptional repression. There are multiple cancer drug candidates that reduce DNA methylation by inhibiting these enzymes. Analysis of the effects of other epigenetic enzymes may yield additional cancer drug targets. ...

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Metazoans regulate biological functions in a number of ways, including via gene expression. Epigenetics is the term for regulation of gene expression, other than via changes in the DNA sequence. Modification of DNA or histones by methylation, acetylation, phosphorylation, and ubiquitination affects gene expression and function. Enzymes that chemically modify genomic DNA and histones, as well as epigenetic chromatin remodeling factors, regulate chromatin accessibility and therefore gene expression. Some chromatin remodeling factors contain a chromatin organization modifier domain, or chromodomain, responsible for ATP hydrolysis-dependent chromatin reorganization. Other protein families regulating chromatin structure include bromodomain proteins, plant homeodomain proteins, and the inhibitor of growth family. During the process of stem cell differentiation into terminally differentiated cells, altered expression of chromatin modification enzyme and chromatin remodeling factor genes changes histone modifications, leading to increases or decreases in gene transcription. For example, histone acetyltransferases add acetyl groups to histones. This histone modification is common during transcriptional activation. Epigenetic enzymes also exhibit different expression profiles in tumor cells relative to normal cells, suggesting a role for DNA methylation and chromatin modification in oncogenesis. For example, tumor suppressor genes are often hypermethylated during cancer, which typically causes transcriptional repression. There are multiple cancer drug candidates that reduce DNA methylation by inhibiting these enzymes. Analysis of the effects of other epigenetic enzymes may yield additional cancer drug targets.